Neocortical neurogenesis: morphogenetic gradients and beyond

Each of the five cellular layers of the cerebral neocortex is composed of a specific number of a single predominant 'class' of projection neuron. The projection neuron class is defined by its unique morphology and axonal projections to other areas of the brain. Precursor cell populations lining the embryonic lateral ventricles produce the projection neurons. The mechanisms regulating precursor cell proliferation also regulate total numbers of neurons produced at specific developmental periods and destined to a specific neocortical layer. Because the newborn neurons migrate relatively long distances to reach their final layer destinations, it is often assumed that the mechanisms governing acquisition of neuronal-class-specific characteristics, many of which become evident after neuron production, are independent of the mechanisms governing neuron production. We review evidence that suggests that the two mechanisms might be linked via operations of Notch1 and p27(Kip1), molecules known to regulate precursor cell proliferation and neuron production.